Internalizing mental disorders are highly comorbid with one another, and evidence suggests that etiological processes contributing to these disorders often overlap. This systematic umbrella review aimed to synthesize meta-analytic evidence from observational longitudinal studies to provide a comprehensive overview of potentially modifiable risk and protective factors across the depressive, anxiety, and eating disorder psychopathology domains. Six databases were searched from inception to August 2022. Only meta-analyses of longitudinal studies that accounted for baseline psychopathology (either via exclusion of baseline cases or statistical adjustment for baseline symptoms) were included. Methodological quality of meta-analyses was evaluated using the AMSTAR 2, and quality of evidence for each analysis was rated using GRADE. Study selection, quality assessment, and data extraction were conducted in duplicate by independent reviewers. The protocol for this review was registered with PROSPERO (CRD42020185575). Sixty-one meta-analyses were included, corresponding to 137 meta-analytic estimates for unique risk/protective factor-psychopathology relationships. Most potential risk/protective factors, however, were examined only in relation to depressive psychopathology. Concern over mistakes and self-esteem were the only risk and protective factors, respectively, identified as statistically significant across depressive, anxiety, and eating disorder psychopathology domains. Eight risk factors and four protective factors also emerged as having transdiagnostic relevance across depressive and anxiety domains. Results suggest intervention targets that may be valuable for preventing/treating the spectrum of internalizing psychopathology and reducing comorbidity. However, few factors were identified as transdiagnostically relevant across all three internalizing domains, highlighting the need for more research investigating similar sets of potential risk/protective factors across internalizing domains.